摘要
目的探讨严重急性呼吸综合征(SARS)冠状病毒N蛋白所致大鼠肺部炎症反应及糖皮质激素(以下简称激素)对其的调节作用。方法24只SD大鼠随机分为4组,每组6只;A组大鼠气管内滴入无菌生理盐水0.2ml,B组(6h)、C组(24h)大鼠气管内滴入SARS病毒N蛋白溶液0.2ml,D组大鼠气管内滴入SARS病毒N蛋白溶液0.2ml的同时腹腔内注射10mg/kg地塞米松。测4组大鼠外周血、支气管肺泡灌洗液(BALF)中WBC总数及分类;测4组大鼠肺组织湿/干(W/D)比值;观察4组大鼠肺组织病理学变化;ELISA测4组大鼠血清及BALF中IL6、IL10、转化生长因子(TGF)β1水平。结果(1)外周血淋巴细胞比例C组较A组低(P<0.05),D组较A、C组均低(P值均小于0.01);D组WBC总数较A、C组均低(P<0.01)。BALF中WBC总数C组较A组高(P<0.05),D组较C组低(P<0.05);B、C组BALF中肺泡巨噬细胞占98%～99%。(2)肺脏W/D比值B、C组较A组高(P<0.05),D组较C组低(P<0.01)。(3)肺组织病理学变化:B、C组大鼠肺泡间隔明显增宽,有较多的炎性细胞渗出,包括中性粒细胞、淋巴细胞、单核细胞、成纤维细胞等,血管充血、淤血,有的支气管腔内有炎性细胞渗出,C组变化较B组无明显加重;D组大鼠肺组织炎性反应较B、C组减轻,肺泡间隔变薄,炎性细胞渗出减少。(4)血清及BALF中IL6、IL10、TGFβ1水平B组较A组高(P<0.01),C组进一步升高(P<0.01),D组较C组低(P<0.01)。结论SARS冠状病毒N蛋白具有致病性,能够引起大鼠肺部炎症反应和(或)急性肺损伤,肺损伤与促炎性细胞因子、抗炎性细胞因子的升高及失衡有关;激素可有效地减轻SARS冠状病毒N蛋白所致的肺部炎症反应。
Objective To study the pulmonary inflammatory reaction induced by N-protein of SARS-CoV in rat models and the effects of glucocorticoids on the inflammatory reaction. Methods The pulmonary inflammatory reaction in rat models were induced by intratracheal instillation of N-protein of SARS-CoV with a dose of 0. 2 mg/kg. The rats were randomly divided into four groups： normal saline control group （Nc group） , N-protein group 1 （P1 group, 6 h） , N-protein group 2（ P2 group, 24 h） , and N-protein ＋ dexamethasone group （ P ＋ D group, dexamethasone 10 mg/kg intraperitoneally ）. The blood samples, bronchial alveolar lavage fluid （BALF） and lung tissue were collected after challenge. The cytological and histopathologic changes of lung tissues were observed and the wet/dry ratios （W/D） of lung tissue were determined. The interleukin（IL） -6, IL-10 and transforming growth factor-β1 （ TGF-β1 ） of serum and BALF were measured by ELISA. Results （ 1 ） Compared with the percentage of peripheral blood lymphocytes in Nc group [ （ 68.42 ± 13.07 ） % ], that in P2 group [ （ 50.50 ± 14. 36 ） % ] was significantly decreased （ P 〈 0. 05 ） ; compared with Nc group and P2 group, that in P ＋ D group was furthermore significantly decreased（ P 〈0.01 ）. Compared with the total WBC of peripheral blood in Nc group[ （5.86 ±2.25） ×10^9] and P2 group [（4.83 ± 1.49） × 10^9] , that in P ＋ D group[ （1.96 ± 1.30） × 10^9] was significantly decreased（P 〈0. 01）. （2） Compared with the total WBC of BALF in Nc group[ （95 ±29） × 10^7 ] , that in P2 group [ （ 160 ± 60） × 10^7 ] was significantly increased （ P 〈 0.05 ） ; but compared with P2 group, that in P ＋ D group [ （ 62 ± 23 ） × 10^7 ] was significantly decreased （ P 〈 0. 05 ）. Analysis of BALF differential cell counts showed that the majority of cells were alveolar macrophages in all groups. （ 3 ） The W/D ratios of lung tissue in both P1 and P2 group[ （5.18 ±0. 29） and
出处
《中华内科杂志》
CAS
CSCD
北大核心
2005年第12期890-893,共4页
Chinese Journal of Internal Medicine
基金
上海市科技发展基金资助项目(03DZ19618)
